The proposed studies will determine the mechanism(s) of the synergistic protective effect of combinations of antibody and interferon (IFN). Our previous studies have indicated that IFNs and virus-specified antibody can act synergistically to inhibit a variety of viruses. My preliminary results indicate that natural crossneutralizing antibody and monoclonal antibodies that block adsorption and penetration and/or uncoating can synergistically inhibit poliovirus and HSV. In addition, our preliminary studies suggest that IgM's protective effect in vivo may be dependent upon IFN. Surprisingly, combinations of crossreacting non-neutralizing monoclonal antibodies and IFN were protective against poliovirus. These findings are significant in that they suggest that some crossreacting non-neutralizing antibodies and low levels of neutralizing antibody may be protective if endogeneous IFN is produced during natural infection. Our studies suggest that the mechanism(s) of this synergistic protective effect of antibody appears to be mediated by IFN. The proposed studies will determine how IFN affects the infectivity of different virus-antibody complexes, affects binding and/or penetration of virus-antibody complexes, affects the efficiency of antibody "neutralization", and/or reduces the "persistent fraction". These studies are significant in that they provide new information on the protective role of crossreacting antibody and on the importance of the combined protective effect of IFN and antibody as an early host defense in controlling primary infections, inhibiting reinfections and inhibiting infection with related viruses. Also, these studies will investigate the natural dependence of different classes of antibody of IFN for their protective effect. Although these studies are concerned with defining the mechanism of the IFN mediate protective effect, the long term goal of these studies is to demonstrate group specific antigen(s) that induce virus specific antibodies that are dependent on IFN for a maximum protective effect. These studies will be important in evaluating the immunoprophylactic potential of and development of subunit viral vaccines and determining the potential usefulness of IFN and antibody combinations in treatment of viral infections.